Detection of rubella cases through the measles laboratory surveillance network in South-East Nigeria: 2020-2024

¹Molecular Virology Laboratory, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu, Nigeria, ²Epidemiology and Health Research Unit, Department of Public Health and Disease Control, Abia State Ministry of Health Umuahia, Abia State, Nigeria, ³Anambra State Ministry of Health, Awka Anambra State, Nigeria, ⁴Ebonyi State Ministry of Health, Abakaliki, Ebonyi State, Nigeria, ⁵Enugu State Ministry of Health, Enugu, Enugu State, Nigeria, ⁶Imo State Ministry of Health, Owerri, Imo State, Nigeria, ⁷Abia State Specialist Hospital Laboratory, Amachara, Abia State, Nigeria, ⁸Imo State Public Health Laboratory, Owerri, Imo State, Nigeria, ⁹World Health Organization (WHO) Country Office, Abuja, Nigeria, ¹⁰Nigerian Centre of Disease Control and Prevention, Abuja, Nigeria

^&Corresponding author
Chinedu Michael Chukwubike, Molecular Virology Unit, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu, Nigeria

Introduction    

Rubella, also known as German measles, is a vaccine-preventable viral infection presenting with a characteristic maculopapular rash, resembling measles in clinical appearance [1-3]. It is an enveloped positive-stranded ribonucleic acid virus that belongs to the genus Rubivirus and family Togaviridae [4]. Laboratory experiments using cultured cells indicate that rubella infection may induce apoptosis in specific cell lines [5]. Clinically, rubella causes a rash-like illness accompanied by lymphadenopathy and low-grade fever [6]. Transmission typically occurs through droplets from respiratory secretions released from infected persons during coughing or sneezing, as well as direct contact [6]. It is a highly contagious disease that poses severe risks during pregnancy [3]. Contracting rubella during early pregnancy, especially in the first trimester, can lead to adverse outcomes like miscarriage, stillbirth, or congenital rubella syndrome (CRS), which is characterized by multiple lifelong disabilities [7]. Both natural infection and vaccination confer long-term immunity [8]. When rubella infection occurs during early pregnancy, the likelihood of CRS in the fetus is estimated to be as high as 90% [8,9]. Due to teratogenicity of rubella virus [3], preventing CRS is the principal objective of rubella vaccination programs [10]. Although a single dose of rubella-containing vaccine (RCV) provides lifelong protection, Nigeria remained among 19 countries that had not introduced RCV into their routine immunization schedule as of the end of 2024 [11]. Modeling studies indicate that integrating RCV into national programs rapidly reduces rubella and CRS incidence, and with adequate coverage, elimination of transmission is achievable [12-14].

Evidence from countries that have introduced RCV into their immunization program has shown a steady decline from 13.9 cases per million to 1.7 cases per million [15]. It was also documented that between 2012 and 2022, the global incidence of rubella saw a dramatic decline of 81%, dropping from 93,816 reported cases to just 17,407, a testament to the growing effectiveness of immunization programs and public health initiatives; during this same period, 98 countries, primarily, middle and high-income countries, successfully eliminated rubella, marking a significant milestone in global disease control and eradication efforts [16].

In Sub-Saharan Africa countries, the overall seroprevalence of rubella remains high [17-19] with studies indicating rates as high as 68% in certain regions like Ethiopia [17]. In Nigeria, where we have limited published research on rubella, there are varied burdens of seroprevalence rates across different areas and populations. A study in Kebbi, Northwestern Nigeria demonstrated a 3.0% prevalence [20] while 82.96% and 2.22% IgG and IgM, respectively, were reported from Jos Plateau State [21]. A study in Abia state, South East Nigeria, reported a 10.7% of rubella IgM [22].

In Nigeria, rubella surveillance has historically been limited, with most cases identified through the measles laboratory surveillance network, which tests for rubella IgM in measles-negative samples. This integrated approach has proven valuable in detecting rubella circulation, especially in regions where rubella-specific surveillance is not yet fully established. The World Health Organization (WHO) recommends leveraging existing measles surveillance platforms to monitor rubella, particularly in resource-constrained settings [23]. The rationale for this study is the urgent need to address rubella critical public health gaps related to rubella and respond to emerging epidemiological data from South East Nigeria. This study provides baseline evidence from the South-East Nigeria on the burden of rubella virus, to inform policymakers on need to introduce RCV and support post-vaccine impact assessment.

Methods     

Study area: this study was conducted in South-Eastern Nigeria, comprising five states: Abia, Anambra, Ebonyi, Enugu, and Imo. These states have a total of ninety-five administrative Local Government Areas. The region spans approximately 29,000 square kilometers and has an estimated population exceeding 25 million, based on recent census projections [24]. It features a mix of urban centers and rural communities, with varying levels of access to healthcare services. The climate in the zone is tropical, with a rainy season lasting from April to October and a dry season from November to March. Average temperatures range between 22°C and 32°C, while annual rainfall typically varies from 1,500 mm to 2,200 mm. These climatic conditions may influence the transmission dynamics of several tropical viral infections, including rubella. Healthcare infrastructure across the region includes primary health centers, general hospitals, privately owned hospitals and tertiary health institutions. However, disparities in service delivery persist, particularly in hard-to-reach areas.

Study design: we conducted a retrospective cross-sectional study utilizing epidemiological surveillance data on measles collected across South-Eastern Nigeria by the respective state disease surveillance team. The data spanned a five-year period, from January 1, 2020, to December 31, 2024, and were obtained through routine case-based surveillance activities coordinated under the Integrated Disease Surveillance and Response (IDSR) framework.

Data collection: this study utilized data collected from about 940 established disease surveillance focal sites distributed across the states in South-East Nigeria. These sites are integrated within the conventional surveillance framework and are situated in designated health facilities encompassing all levels of healthcare delivery. Each focal site is overseen by a trained surveillance officer referred to as focal person, whose task is in the identifying and reporting suspected cases of febrile rash illnesses, primarily measles and rubella to the Local Government Area Disease Surveillance and Notification Officer (LGA DSNO). Upon receipt of a report, the DSNO initiates case investigation following standard operating procedures (SOPs), which includes the collection of blood samples and completion of standardized case investigation form (CIF) /IDSR Form. Case definitions are by following SOPs and vary by context. At the health facility level, a suspected measles or rubella case is defined as any individual presenting with fever and maculopapular rash, accompanied by one or more of the following symptoms: cough, coryza, or conjunctivitis. Alternatively, a case may be defined based on clinical suspicion by a clinician or healthcare provider. At the community level, the definition is simplified to any individual presenting with fever and rash [25]. In addition to facility-based surveillance, a complementary community-based reporting mechanism exists, whereby trained community health informants notify focal persons of suspected cases. In some instances, reports are made directly to the LGA DSNO. Venous blood samples (3-5ml) were collected from suspected cases under aseptic conditions. After clotting, serum was separated into sterile cryovial tubes, appropriately labeled and stored at -200C. Collected serum samples are transported to the WHO / Nigeria Center for Disease Control and Prevention (NCDC) accredited regional measles reference laboratory for South East Nigeria at Molecular Virology Laboratory, Microbiology Department, University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla Enugu Nigeria for quality control, serological testing, archiving of samples and quarterly transfer of 10% of both positive and negative samples to Pasteur Institut of Cote d´Ivoire department of epidemic virus, respiratory virus unit, for further external quality assurance. The UNTH Molecular Virology Laboratory has consistently achieved 100% proficiency scores in the external quality assessments from 2020 to 2024 as conducted by WHO Regional Measles Reference Laboratory at Victorian Infectious Diseases Reference Laboratory, Australia. The laboratory performs IgM antibody enzyme-linked immunosorbent assay (ELISA) detection for measles and rubella in accordance with World Health Organization (WHO) protocols and quality standards [23]. Laboratory findings are communicated weekly to WHO, NCDC and respective State Ministry of Health (MOH) to inform public health response and policy. In suspected cases of “outbreaks”, results are shared immediately for response activities.

Case selection: all suspected cases of rubella reported between January 1, 2020 and December 31, 2024 across South East Nigeria were included in this study. Inclusion and Exclusion Criteria: Suspected rubella cases are individuals notified as suspected measles cases whose serum samples tested negative or borderline for measles IgM antibodies using ELISA. Confirmed rubella cases are individuals whose serum samples tested positive for rubella-specific IgM antibodies by ELISA.

Data management and analysis: we conducted all data analyses using Microsoft Excel 2019 and SPSS version 27. Data cleaning was carried out by the researcher in collaboration with the state disease control surveillance team using Microsoft Excel. The cleaned dataset was then exported to SPSS for further analysis. We applied descriptive statistical methods to examine the epidemiology of rubella cases, focusing on variables such as age, sex, month and years samples were collected and state of residence. We grouped variables: sex was classified as either male or female. Age was grouped into: under 1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years, and 20 years and above. Limited number of data points were missing, and these were indicated within the tables. We analyzed the distribution of rubella cases using frequencies, percentages, and proportions. Descriptive statistics were used to present frequencies and percentages, while bivariate analysis assessed associations between variables, with significance set at p < 0.05. The findings were presented through tables and graphs to highlight key patterns and trends.

Ethical considerations: this study was based on routine surveillance data collected as part of the national IDSR system. As such, formal ethical approval was not required. However, permission to access and analyze the data was obtained from the respective MOH in South-East Nigeria. All data used for analysis were anonymized prior to extraction, ensuring that no personal identifiers were retained. The datasets were stored on a password-protected computer, accessible only to authorized members of the research team, in accordance with standard data protection protocols.

Results     

Out of 7,257 suspected measles cases collected between January 1, 2020 and December 31, 2024 from the five South-Eastern Nigerian States, a total of 6,145 cases were eligible for rubella IgM analysis. Among these, 742 cases (12.1%) tested positive for rubella IgM, 5343 cases (86.9%) were negative while 60 (1.0%) were borderline (Table 1). Gender based analysis showed that 52.3% (n = 388) of the positive cases were females, while males comprised 47.4% (n=) of 352 cases but there was no statistically significant difference observed in rubella incidence between genders (p = 0.352). Of the rubella confirmed cases, 97.2% (721/742) had information on age. The median age for rubella infection in South East Nigeria was 3 years (IQR: 3-7 years). The age distribution revealed that infants under one year significantly had the highest rate of rubella IgM positivity, accounting for 39.9% of all positive cases (p<0.001). This was followed by children aged 5 to 9 years (23.5%) and those aged 1 to 4 years (19.4%). Positivity rates declined steadily in older age groups: 10 to 14 years (6.7%), 15 to 19 years (2.8%), and adults aged 20 years and above showed 4.9% rate. Children under 10 years of age make up over 80% of all positive cases (Table 1). The annual trend in rubella IgM positivity has revealed statistically significant variations over the five-year surveillance period, with the highest rate observed in 2020 at 279 cases (37.6%). This was followed by a sharp decline in 2021 with only 20 cases (2.7%), a slight increase was observed in 2022 at 40 cases (5.4%), and a notable resurgence in 2023 and 2024 with 190 cases (25.6%) and 213 cases (28.7%) respectively (p<0.01). Over the five years, the annual average rubella was 148 cases per year (p<0.01) (Table 1).

State-wise distribution of rubella IgM antibody testing across five states in southeastern Nigeria revealed notable variations in seropositivity. Enugu State recorded the highest positivity rate, with 198 out of 1,396 suspected cases testing positive (26.7%), corresponding to a seropositivity burden of 42.2 per 1,000,000 population. Anambra followed with 167 positive cases out of 1,452 tested (22.5%) and a seropositivity rate of 28.1 per million. Abia State reported 152 positive cases from 1,394 samples (20.5%), yielding a seropositivity of 36.7 per million. Imo State had 143 positives out of 1,173 cases (19.3%), with a seropositivity rate of 26.2 per million. Ebonyi State recorded the lowest positivity rate, with 82 out of 730 cases testing positive (11.1%) and a seropositivity of 25.3 per million (Table 2). Monthly rubella IgM positivity from January 2020 to November 2024 revealed a major peak in January 2020. The positivity rate remained low throughout 2021 and early 2022. Smaller spikes were observed between March and June 2023, and again from February to April 2024). These range from 6.44 per 1,000,000 in February, 8.48 per 1,000,000 in March, 3.9 per 1,000,000 in April. Overall, the data showed a recurrent seasonal pattern, with higher positivity consistently occurring in the first quarter (January, February, March and April) of each year (Figure 1).

Figure 2 illustrates a fluctuating monthly distribution of rubella cases across the various states in South-Eastern Nigeria from 2020 to 2024. The highest incidence across the states was recorded in the first quarter of 2020, followed by a marked decline throughout 2021 and 2022. During this period, several states reported zero cases in certain months. However, rubella cases began to rise again in 2023 and persisted into 2024, with intermittent spikes observed in specific months and states. Out of the 388 females who tested positive for rubella IgM in South East Nigeria, 27 (7.0%) were within the childbearing age range of 15-45 years. The state-wise distribution of these cases varied across the states: Abia State accounted for 30.0% (8/27), Anambra State 11.1% (3/27), Ebonyi State 18.5% (5/27), Enugu State 7.4% (2/27), while Imo State recorded the highest proportion with 33.3% (9/27).

Discussion     

The measles surveillance laboratory database from South East Nigeria, 2020 to 2024, has shown that rubella is endemic in the region and circulates in all the states within the zone. The findings reveal important epidemiological patterns that highlight the public health significance of rubella surveillance, especially in regions where there may be measles and rubella co-infection and where a rubella-containing vaccine has yet to be introduced into the immunization program.

Between 2020 and 2024, a total of 6,145 febrile rash cases were reported from the zone, of which 742 (12.1%) were serologically confirmed as rubella IgM-positive. This prevalence mirrors the 12.1% reported in Ethiopia´s national measles-rubella surveillance [26] and closely aligns with the 10.7% confirmation rate documented in Aba, Abia State, South-Eastern Nigeria [22]. However, our findings exceed the 2.9% rubella positivity reported in a North-Western Nigerian state [21], yet remain lower than rates observed in other African countries: 16.7% in Côte d´Ivoire [27], 33.6% in South Africa prior to rubella vaccine introduction [28], and 49.5% in the Central African Republic [29]. Rubella IgM positivity varied across regions, with higher rates observed in countries that had not introduced rubella vaccination at the time of their studies, such as Cote d´Ivoire, South Africa, and the Central African Republic. These differences may likely be attributed to ongoing natural transmission in unvaccinated populations, as well as possible disparities in surveillance systems, and other socio-demographic factors. These variations underscore the regional disparities in rubella burden and highlight the need for immunization strategies.

Gender-based analysis of rubella IgM-confirmed cases in this study revealed a modest predominance among females (52.3%) compared to males (47.4%). This trend is consistent with findings from Aba, Abia State Nigeria [22], where 12.9% of females and 8.6% of males tested positive for rubella IgM. Similar female predominance was also reported in other studies, including 54.3% female versus 45.6% male positivity in Jos, Plateau State (North-Central Nigeria) [21], 53.8% versus 46.2% in the Central African Republic [29], and 53.2% female versus 43.5% male in South Africa [29]. These patterns suggest a recurring gender disparity in rubella IgM seropositivity across diverse geographic settings.

Analysis of five years of surveillance data revealed that rubella IgM-confirmed cases were highest among children under one year of age, accounting for about 40.0% of all positive cases. Furthermore, children under 10 years constituted over 80% of confirmed rubella cases. This age-related distribution aligns with findings from Northwestern Nigeria [20], where 58% of rubella IgM-positive cases occurred in children under five years. Similarly, studies from the Central African Republic [29] and South Africa [28] reported that 58.2% and 87% of confirmed cases, respectively, were among children younger than 10 years. However, a previous study from Southeastern Nigeria [22] indicated a slightly older age distribution, with most confirmed cases occurring in children aged 5 to 14 years. The predominance of rubella IgM-confirmed cases among children under one year of age (40%) in this study is particularly concerning in a setting where rubella vaccination has not yet been introduced. This early-age vulnerability observed in this study may reflect ongoing community transmission and a lack of maternal immunity, exposing infants to infection either congenitally or shortly after birth. The finding underscores the urgent need for rubella vaccine introduction into the national immunization schedule to prevent congenital rubella syndrome (CRS) and reduce early childhood morbidity.

Seasonal analysis revealed a consistent pattern of increased rubella IgM positivity during the first quarter of each year. This trend aligns with previous study indicating that rubella transmission often peaks during cooler months in tropical climates [21]. The seasonal variation observed suggests that rubella outbreaks occurred at different times across states, likely influenced by local transmission dynamics. Similar to findings from South Africa [28], these regional differences may reflect transmission in settings such as communities, hospitals, and schools [21]. The clustering of cases and temporal variations in the South-Eastern Nigerian States may be attributed to case accumulation and high contact rates within a population lacking rubella vaccination. Comparable observations have been reported in other unvaccinated populations, further underscoring the need for targeted immunization strategies [21,28].

Out of the 388 females who tested positive for rubella IgM in South East Nigeria, 27 (7.0%) were within the childbearing age range of 15-45 years. This finding is particularly significant given the risk of congenital rubella syndrome (CRS) in pregnant women infected with rubella. These findings align with observations made by other researchers in Nigeria and across sub-Saharan Africa. In Ilorin (North Central Nigeria), for example [30] found that about 8.1% of women of reproductive age tested positive for rubella IgM, suggesting recent or ongoing infections. Similarly, [31] reported a 7.8% positivity rate among pregnant women in Rivers State (South South Nigeria), which is strikingly close to what we observed here. In Ado-Ekiti (South West Nigeria), [32] noted an even higher rate 12%. Taken together, these studies paint a consistent picture: rubella is still circulating among women of childbearing age in Nigeria, and without routine vaccination, the risk of congenital rubella syndrome remains a real concern. Limitations of the study: This study faced several limitations, including reliance on passive measles surveillance (which might result in missing rubella cases without rash or fever), incomplete demographic data, and geographic restriction to South East Nigeria. The absence of molecular diagnostics like RT-PCR limited the confirmation and genotyping of circulating rubella cases. Despite these challenges, the findings provide a vital foundation for future research and highlight the need for more diagnostics, broader surveillance, and vaccine introduction in Nigeria.

Conclusion     

Rubella remains endemic in South-Eastern Nigeria, with consistent circulation across all states between 2020 and 2024. Of the 6,145 febrile rash cases, 12.1% were confirmed rubella IgM-positive, a rate comparable to other African countries lacking routine rubella vaccination. Most cases occurred in children under 10 years, especially infants under one, highlighting early vulnerability and the absence of maternal immunity. Females showed slightly higher positivity rates, and 7% of confirmed cases were among women of childbearing age, raising concerns about congenital rubella syndrome (CRS). Seasonal peaks in the first quarter of each year and regional clustering suggest transmission is influenced by local dynamics and high-contact settings. These findings underscore the urgent need to introduce rubella-containing vaccines into Nigeria´s national immunization schedule and strengthen surveillance efforts.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Chinedu Michael Chukwubike, Chioma Uju Benjamin-Puja, Constance Ugochi Azubuike, Chioma Chinyere Edu-Alamba, Princess Ada Ojeanya, Jennifer Ifeoma Ajaegbu, Chinenye Ibeh, Elezuo Okorie Elezuo, Chuma Emembolu, Ogbonna Nwabeke, Okechukwu Ogbodo, Hyacinth Egbuna, Oluchi Obioma Adighogu, Okudoh Chika David, Roseline Adolphus-Chukwuemeka, Leonard Ikedioha, Salihu Abudullahi, Blessing Ekanem, Martin Chukwuji, Olajumoke Babatunda, Mary Indyeriyo-Kaan Dooshima oversaw data collection. Chinedu Michael Chukwubike, Chioma Uju Benjamin-Puja, Constance Ugochi Azubuike, Chioma Chinyere Edu-Alamba, Princess Ada Ojeanya, Jennifer Ifeoma Ajaegbu, Chinenye Ibeh performed laboratory analysis, quality control and data interpretation. Chinedu Michael Chukwubike, Chioma Uju Benjamin-Puja, Constance Ugochi Azubuike and Chioma Chinyere Edu-Alamba performed data analysis and visuals. Chinedu Michael Chukwubike, Chioma Uju Benjamin-Puja, Constance Ugochi Azubuike, Chioma Chinyere Edu-Alamba, Princess Ada Ojeanya, Jennifer Ifeoma Ajaegbu, Chinenye Ibeh, Elezuo Okorie Elezuo, Chuma Emembolu, Ogbonna Nwabeke, Okechukwu Ogbodo, Hyacinth Egbuna, Oluchi Obioma Adighogu, Okudoh Chika David, Roseline Adolphus-Chukwuemeka, Leonard Ikedioha, Salihu Abudullahi, Blessing Ekanem, Martin Chukwuji, Olajumoke Babatunda, Mary Indyeriyo-Kaan Dooshima drafted the final manuscript and contributed to all sections of the manuscript. All authors read and approved the final manuscript.

Acknowledgments     

We acknowledge with gratitude the contributions of the Local Government Area (LGA) Disease Surveillance and Notification Officers (DSNOs), Community Health Informants, and the State Epidemiology Team for their role in data collection and reporting. We also thank the World Health Organization (WHO) and the Nigeria Centre for Disease Control (NCDC) for their technical support.

Table and figures     

Table 1: distribution of rubella IgM seropositivity in South East Nigeria - 2020 to 2024

Table 2: state level distribution of rubella IgM positivity in South East Nigeria on population estimates

Figure 1: cumulative monthly distribution of rubella cases in South East Nigeria - 2020 to 2024

Figure 2: monthly distribution of rubella cases within the five South East Nigerian State

References